Proteolytic activation of the interleukin-1beta precursor by Candida albicans.
Chronic inflammation rather than invasion is characteristic of some forms of superficial candidiasis such as denture stomatitis. We hypothesized that Candida albicans may play a critical role in the pathogenesis of inflammatory lesions observed in chronic candidiasis by activating the proinflammatory cytokine interleukin-1beta (IL-1beta) from epithelial stores of the precursor. The aim of this study was therefore to demonstrate the proteolytic cleavage and activation of the inactive precursor of IL-1beta (pro-IL-1beta) by C. albicans. After incubation of either blastospores or hyphae with the inactive precursor, proteolytic cleavage was monitored by sodium dodecyl sulfate-polyacrylamide gel electrophoresis Western immunoblotting analysis, and the biological activity of the cleavage products was tested in a bioassay. We report here that late-stationary-growth-phase blastospores as well as hyphae of C. albicans, but not exponentially growing cells, can efficiently cleave pro-IL-1beta to yield fragments of molecular masses compatible with mature biologically active IL-1beta (17 to 19 kDa). Assays conducted in the presence of selected proteinase inhibitors suggest that the cleavage of pro-IL-1beta involves the participation of one or more aspartyl proteinases. Cleavage products showed a dose-dependent IL-1beta-like activity in a thymocyte proliferation bioassay, which was inhibited by anti-IL-1beta neutralizing antibodies. The present data thus suggest a role for C. albicans proteinases in the activation and maintenance of the inflammatory response at epithelial surfaces.
Beauséjour
A
A
Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire et Faculté des Sciences et de Génie, Université Laval, Québec, Canada.
Grenier
D
D
Goulet
J P
JP
Deslauriers
N
N
D002176:Candida albicans / Q000378:metabolism*; D010450:Endopeptidases / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007375:Interleukin-1 / Q000378:metabolism*; D008970:Molecular Weight; D011498:Protein Precursors / Q000378:metabolism*
D007375:Interleukin-1; D011498:Protein Precursors; C043830:interleukin 1 precursor; D010450:Endopeptidases